Efficacy of NOX-H94 on Anemia of Chronic Disease in Patients With Cancer

Anemia of Chronic Disease Clinical Trial

Official title:

Phase IIa Study to Characterize the Effects of the Spiegelmer® NOX H94 on Anemia of Chronic Disease in Patients With Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01691040
• Other study ID #: SNOXH94C201
• Secondary ID: 2012-001525-27
• Status: Completed
• Phase: Phase 2
• First received: September 4, 2012
• Last updated: June 25, 2014
• Start date: September 2012
• Est. completion date: December 2013

Study information

• Verified date: June 2014
• Source: NOXXON Pharma AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareRomania: National Agency for Medicines and Medical DevicesBulgaria: Bulgarian Drug Agency
• Study type: Interventional

Clinical Trial Summary

This study is conducted to determine the safety, tolerability, and efficacy of NOX-H94 in patients with anemia of chronic disease (ACD). Furthermore, this study is intended to provide data needed to correlate plasma concentrations of NOX-H94 with its efficacy and to choose the appropriate dose and dose schedule of subsequent efficacy studies.

Some chronic diseases, e.g. tumors, inflammation, renal disease, are associated with high hepcidin concentrations in the blood. These hepcidin concentrations cause a reduction in iron concentrations in the blood and subsequently impair formation of red blood cells. Treatment with NOX-H94 is expected to inhibit this patho-mechanism by binding and inactivating hepcidin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent

• Female or male aged >18 years

• Clinically significant anemia of chronic disease (ACD) attributed to histologically or cytologically proven malignancy, either hematological or solid tumor, of any grade or stage: Hemoglobin (Hb) 7.0 g/dL to 10 g/dL, Transferrin saturation (TSAT) <50%, Serum iron <50 µg/dL (SI: <9.0 µmol/L), AND Ferritin >30 ng/mL (SI: >30 µg/L)

• Previous treatment with systemic anti-cancer therapy / regimen

• Eastern Cooperative Oncology Group (ECOG) performance status of =2

• Estimated life expectancy =12 weeks

• Men must agree to follow effective contraception methods during treatment and for 3 months after completion of treatment. Women of childbearing potential must agree to use two forms of effective contraception during treatment and for 3 months after completion of treatment.

Exclusion Criteria:

• Inability to personally provide written informed consent or to understand and collaborate throughout the study

• History of pure red cell aplasia, thalassemia major or sickle cell disease History of anemia unrelated to cancer <10 g/dL within 6 months prior to screening

• Uncorrected iron deficiency

• Regular need for blood transfusions at intervals <6 weeks

• Acute or myeloid leukemia

• Known or suspected chronic bleeding

• Tumor with gastro-intestinal involvement without negative test for fecal occult blood

• Suspected or known history of hemochromatosis

• Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C

• Impaired liver function with bilirubin =2.0 mg/dL (26 µmol/L), AST or ALT =2 times upper limit

• History or risk of significant hepatic disease, e.g. chronic alcohol abuse, hepatic steatosis, hepatic cirrhosis, or organ transplantation

• Severe renal impairment: estimated glomerular filtration rate (eGFR) <30 mL/min (Cockcroft-Gault)

• Known central nervous system malignancy or metastasis

• Significant cardiac disease (e.g. uncontrolled hypertension: systolic blood pressure [BP] >150 mmHg or diastolic BP >100 mmHg; myocardial infarction or unstable angina pectoris) within 6 months prior to screening

• Positive pregnancy test (serum ß-hCG at screening, urine pregnancy test prior to first treatment) or lactation

• Previous participation in this study or treatment with an investigational agent <21 days prior to treatment start

• Hemolysis or bleeding >500 mL (measured or estimated) within 6 weeks prior to treatment start

• Treatment with erythropoiesis-stimulating agents (ESAs) or red blood cell (RBC) transfusions <21 days prior to treatment start

• Cytotoxic anti-tumor treatment <21 days prior to treatment start or planned during the anticipated study period (within 3 months from treatment start or randomization). Maintenance therapy is permitted throughout the study (e.g. lenalidomide, interferon)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia of Chronic Disease
• Chronic Disease

Intervention

Drug:
• NOX-H94
intravenous injection
• Placebo solution
intravenous injection

Locations

Country	Name	City	State
Austria	University Hospital	Graz
Austria	AKH Vienna	Vienna
Austria	Wilhelminenspital	Vienna
Bulgaria	University Hospital	Plovdiv
Bulgaria	Tokuda Hospital	Sofia
Bulgaria	University Hospital	Varna
Romania	Spitalul Judetean	Brasov
Romania	Institutul Oncologic	Cluj-Napoca
Romania	Spitalul Municipal	Craiova
Romania	Spitalul Judetean	Targu-Mures
Romania	Oncomed	Timisoara

Sponsors (1)

Lead Sponsor	Collaborator
NOXXON Pharma AG

Countries where clinical trial is conducted

Austria,  Bulgaria,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory analyses	Soluble transferrin receptor	Treatment start to 1 week after end of treatment	No
Other	Exploratory analyses	Reticulocyte hemoglobin content	Treatment start to 1 week after end of treatment	No
Primary	Response rate of anemia	• Hb increase =1 g/dL OR reticulocyte index normalization (=1%) at any time point until 1 week after the end of treatment; AND absence of all of the following treatment failure criteria until 1 week after the end of treatment: Erythrocyte transfusion, ESA or IV iron,; Hb drop by =1 g/dL; Treatment interruption due to adverse events (AEs)	treatment start to 1 week after treatment end	Yes
Secondary	Response	Proportion of treatment responders at study visits V4, V6, V8, and V10 to V14, as defined for the primary efficacy endpoint	Treatment start to 8 weeks after end of treatment	Yes
Secondary	Failure	Proportion of treatment failures at study visits V4, V6, V8, and V10, as defined for the primary efficacy endpoint	Treatment start to 1 week after end of treatment	Yes
Secondary	Safety and tolerability	Adverse events, Safety signals derived from laboratory diagnostics, vital signs.	Treatment start to 8 weeks after end of treatment	Yes
Secondary	Pharmacokinetics	NOX-H94 plasma concentrations	Treatment start to 8 weeks after end of treatment	No
Secondary	Reticulocytes	Absolute values and change from baseline	Treatment start until 8 weeks after end of treatment	No
Secondary	Red blood cells	Absolute values and change from baseline	Treatment start until 8 weeks after end of treatment	Yes
Secondary	Transferrin	Absolute concentrations and change from baseline	Treatment start to 8 weeks after end of treatment	No
Secondary	Serum iron	Absolute concentrations and change from baseline	Treatment start to 8 weeks after end of treatment	No
Secondary	Ferritin	Absolute concentrations and change from baseline	Treatment start to 8 weeks after end of treatment	No
Secondary	Transferrin saturation	Absolute concentrations and change from baseline	Treatment start to 8 weeks after end of treatment	No
Secondary	Hemoglobin	Absolute concentrations and change from baseline	Treatment start to 8 weeks after end of treatment	Yes